PT  - JOURNAL ARTICLE
AU  - William Barrie
AU  - Yaoling Yang
AU  - Kathrine E. Attfield
AU  - Evan Irving-Pease
AU  - Gabriele Scorrano
AU  - Lise Torp Jensen
AU  - Angelos P. Armen
AU  - Evangelos Antonios Dimopoulos
AU  - Aaron Stern
AU  - Alba Refoyo-Martinez
AU  - Abigail Ramsøe
AU  - Charleen Gaunitz
AU  - Fabrice Demeter
AU  - Marie Louise S. Jørkov
AU  - Stig Bermann Møller
AU  - Bente Springborg
AU  - Lutz Klassen
AU  - Inger Marie Hyldgård
AU  - Niels Wickmann
AU  - Lasse Vinner
AU  - Thorfinn Sand Korneliussen
AU  - Martin Sikora
AU  - Kristian Kristiansen
AU  - Santiago Rodriguez
AU  - Rasmus Nielsen
AU  - Astrid K. N. Iversen
AU  - Daniel J. Lawson
AU  - Lars Fugger
AU  - Eske Willerslev
TI  - Genetic risk for Multiple Sclerosis originated in Pastoralist Steppe populations
AID  - 10.1101/2022.09.23.509097
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.09.23.509097
4099  - http://biorxiv.org/content/early/2022/09/26/2022.09.23.509097.short
4100  - http://biorxiv.org/content/early/2022/09/26/2022.09.23.509097.full
AB  - Multiple sclerosis (MS) is a modern neuro-inflammatory and -degenerative disease, which is most prevalent in Northern Europe. Whilst it is known that inherited risk to MS is located within or within close proximity to immune genes it is unknown when, where and how this genetic risk originated. By using the largest ancient genome dataset from the Stone Age, along with new Medieval and post-Medieval genomes, we show that many of the genetic risk variants for MS rose to higher frequency among pastoralists located on the Pontic Steppe, and were brought into Europe by the Yamnaya-related migration approximately 5,000 years ago. We further show that these MS-associated immunogenetic variants underwent positive selection both within the Steppe population, and later in Europe, likely driven by pathogenic challenges coinciding with dietary and lifestyle environmental changes. This study highlights the critical importance of this period as a determinant of modern immune responses and its subsequent impact on the risk of developing MS in a changing environment.Competing Interest StatementThe authors have declared no competing interest.